期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 99, 期 2, 页码 602-607出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.022412699
关键词
-
资金
- NCI NIH HHS [CA-65838] Funding Source: Medline
- NHLBI NIH HHS [HL-59887] Funding Source: Medline
- NIDDK NIH HHS [DK-56635, R01 DK056635] Funding Source: Medline
We have previously reported the structure of a chromatin remodeling complex (PYR complex) with Ikaros as its DNA binding subunit that is specifically present in adult murine and human hematopoietic cells. We now show that homozygous Ikaros knockout (null) mice lack the PYR complex, demonstrating the requirement for lkaros in the formation of the complex on DNA. Heterozygous lkaros null mice have about half as much PYR complex, indicating a dosage effect for both lkaros and PYR complex. We also show that lkaros null mice have multiple hematopoietic cell defects including anemia and megakaryocytic abnormalities, in addition to previously reported lymphoid and stem cell defects. The null mice also have a delay in murine embryonic to adult beta-globin switching and a delay in human gamma to beta switching, consistent with a previously suggested role for PYR complex in this process. Lastly, cDNA array analyses indicate that several hematopoietic cell-specific genes in all blood lineages are either up- or down-regulated in 14-day embryos from lkaros null as compared with wild-type mice. These results indicate that lkaros and PYR complex function together in vivo at many adult hematopoietic cell-specific genes and at intergenic sites, affecting their expression and leading to pleiotropic hematopoietic defects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据